Radiological contrast administration is still
one of the most common iatrogenic causes of acute renal failure acquired in
the hospital 1-4. Although the pathogenesis of such condition is
still not totally understood, it seems to be due to medullary ischemia caused
by decreased renal blood flow 1-4.

Intravenous fluids, mannitol and furosemide,
have been recommended to prevent radiological contrast-induced nephropathy,
but the efficacy them has not yet been proven 5. Recently, intravenous
acetylcysteine (150 mg.kg-1) 30 minutes before radiological contrast
administration has been indicated, followed by 50 mg.kg-1 four hours
after radiological procedure. Both acethylcystein doses were diluted in 500
mL saline. Results have shown renal protection against nephrotoxicity caused
by radiological contrast.

The incidence of nephropathy by radiological
contrast may reach much higher values In the presence of predisposing factors,
among them: dehydration, diabetes mellitus, multiple mieloma, advanced age,
heart disease, use of diuretics, renal failure and exams with radiological contrast
performed in short time periods 2,8,9.

Radiological contrast during anesthesia may be
intra-arterially injected for diagnostic purposes. So, the understanding of
acute and immediate effects of radiological contrast on major renal functions
is critical.

This study aimed at evaluating acute effects
of radiological contrast in fluid restriction states. For this purpose, the
experiment was performed with dogs under fluid restriction to evaluate immediate
renal and cardiovascular effects after intra-arterial injection of high osmolarity
radiological contrast.

At experiment end, fragments of the left kidney
were removed for histological exam. These fragments were formalin fixed processed
for inclusion in paraffin and stained with hematoxylin-eosin. Sections were
examined by the pathologist who diagnosed type and intensity of pathological
injury.

Mean (x) and standard deviation (s) were calculated
for each variable in each moment and fully randomized factorial analysis of
variance was used with the following tests: interaction between group and moment,
group effect and moment effect. In all tested hypothesis, F were considered
significant when p < 0.05. Contrasts between pairs of means were analyzed
by Tukey's test, with calculation of minimum significant difference for alpha
= 0.05.

RESULTS

Groups were homogeneous in weight and gender.

There has been significant increase in heart
rate (Table I), sodium
clearance (G1 < G2 in M3 and M4) (Table
II) and sodium urinary excretion (G1 < G2 in M2, M3 and M4) (Table
II) for both groups. There has also been significant decrease in urinary
osmolality (Table II),
urinary volume and plasma potassium (G1 < G2 in M3 and M4) (Table
II) for both groups.

In both groups there were animals with normal
histological analysis or with interstitial mononuclear inflammatory infiltrate
in renal cortical, or else, tubular necrosis focuses evidenced by karyolysis
areas.

DISCUSSION

Sodium thiopental and fentanyl were administered
in continuous infusion to provide uniform conditions throughout the experiment,
preventing both overdose and concentrations below therapeutic levels. Urinary
osmolality has decreased for both groups soon after saline or radiological contrast
infusion, but its values remained high. These high osmolality values have shown
that fluid restriction was enough to promote extracellular volume contraction.

Some studies have shown temporary hypertension
after radiological contrast injection 10-11. There have been no changes
in this parameter in our study, similar to another study 12, but
there was increased heart rate and urinary output. There has been temporary
hematocrit decrease after radiological contrast infusion. This result has been
also observed by different studies 9,13,14, and may be attributed
to the osmotic effect of the solution in the contrast.

There are reports 15,16 proving RBF
and ERPF increase in dogs anesthetized with fentanyl. In both groups, there
has been temporary RBF and ERPF increase which was however significant only
for the 0.9% saline group. Possible explanation for our results would be the
anesthetic technique. While previous studies have used bolus injection, we have
used fentanyl in continuous infusion.

Temporary increase in RBF and GFR after 2 or
4 mL.kg-1 contrast have been shown 17. After 8 mL.kg-1,
no changes in RBF were found, but there has been decrease in GFR. In our study,
GFR has also decreased. As to RBF, different results may be attributed to different
methods used by both studies. While the first study 17 evaluated
RBF by flowmetric method, our research has used PAH clearance method. In the
flowmetric technique, results is immediate, while with the clearance method,
result is the mean of what has happened during 30 minutes.

In this latter method, fugacious results with
low clinical significance are not detected. In agreement with this study, a
different study 12 has not found RBF changes but has observed GFR
decrease after radiological contrast injection. In our study, there have been
RBF decrease and RVR increase after contrast injection, being significant in
the final moment and showing that contrast injection has promoted only late
changes.

FF has temporarily decreased after radiological
contrast and similar result was obtained by Katzberg et al. 18. Several
studies have also shown decreased creatinine clearance after low or high osmolality
radiological contrast 3,19,20, or also temporary decrease of this
parameter after contrast 19,21. Some authors have used plasma creatinine
(PCr) as parameter for evaluating renal function. There has been
PCr increase when radiological contrast was simultaneously administered
with furosemide 22,23 or mannitol 23, in patients with
normal or increased baseline PCr3 and in patients with
renal failure alone or associated to diabetes mellitus 24. A different
study has shown that PCr was not significantly changed after radiological
contrast 25. The difference in those studies might have been hydration,
of there might have been GFR decrease although not so significant to increase
PCr.

Another hypothesis to explain radiological contrast
effects on renal hemodynamics would be the possibility of hyperosmotic solutions
stimulating rennin-angiotensin system 28. It has been shown 29
that hypertonic solutions injected in the renal artery of dogs would promptly
promote major increase in rennin release.

UV and Cosm have significantly increased
soon after radiological contrast injection, but Cosm has returned
to baseline levels at the end of the experiment. There has also been temporary
CH2O decrease.

Literature is controversial with regard to urinary
volume since there are studies 19,30 showing its decrease after radiological
contrast, while others 10,12,13 have shown increase in this parameter,
similarly to our study. Also in line with our study, a different research 13
has shown increased Cosm after radiological contrast injection.

Both groups have shown increased CNa+,
UENa+ e PK+ while in the radiological contrast group there
has also been increased FENa+ and decreased UNa+ and UK+.
The two latter could be explained by osmotic diuresis-induced dilution. Some
studies, in agreement with ours, have shown increased UENa+ 12,31,32
and FENa+ 32 after ionic and non-ionic radiological contrast,
which seems to be independent of contrast osmolality. Increased sodium excretion
cannot be explained by sodium content in radiological contrast: diatrizoate
has high sodium concentration, while ioxilan, iopamidol, iohexol and other low
osmolality contrasts have very low concentrations of this electrolyte. A possible
explanation for increased sodium urinary excretion could be osmotic diuresis
promoted by all radiological contrasts, regardless of sodium content and of
radiological contrast being or not hyperosmotic.

Potassium is primarily excreted by kidneys and
the rate is a direct function of this ion overload in the body. Also, when sodium
is too high in the tubular lumen, there is sodium entrance in the tubular cell
and sodium pump stimulation with potassium entering the cell and then being
excreted in the tubular lumen 33. This may explain decreased plasma
potassium in the two final moments in both groups in our experiment.

There has been no difference between groups in
pathological findings. Both groups presented normal histological analysis or
interstitial inflammatory infiltrate of mild to severe intensity or tubular
necrosis focuses.

One of the first studies performed in our Department
34 has found, in most dogs, histological changes compatible with
chronic pyelonephritis. The author has concluded that, in dogs, chronic pyelonephritis
is a frequent pathological diagnosis. Similar pathological result obtained for
both groups has shown that there were no radiological contrast-induced renal
injuries.

So, in the conditions of this study, intra-arterial
radiological contrast in animals with decreased extracellular volume has promoted
a two-phase effect on renal function. Initially it promoted increased diuresis
and sodium excretion, but then the hemodynamic conditions impaired and, as a
consequence, renal function impaired, with increased renal vascular resistance
and decreased glomerular filtration rate.